Pompe disease gene therapy

Authors

Barry j. Byrne, University of Florida, United States
Darin J. Falk, University of Florida, United States
Christina A. Pacak, Children's Hospital Boston, United States
Sushrusha Nayak, University of Florida, United States
Roland W. Herzog, University of Florida, United States
Melissa E. Elder, University of Florida, United States
Shelley W. Collins, University of Florida, United States
Thomas J. Conlon, University of Florida, United States
Nathalie Clement, University of Florida, United States
Saleem Islam, University of Florida, United StatesFollow

Document Type

Article

Department

Paediatric Surgery

Abstract

Pompe disease is an autosomal recessive metabolic myopathy caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase and results in cellular lysosomal and cytoplasmic glycogen accumulation. A wide spectrum of disease exists from hypotonia and severe cardiac hypertrophy in the first few months of life due to severe mutations to a milder form with the onset of symptoms in adulthood. In either condition, the involvement of several systems leads to progressive weakness and disability. In early-onset severe cases, the natural history is characteristically cardiorespiratory failure and death in the first year of life. Since the advent of enzyme replacement therapy (ERT), the clinical outcomes have improved. However, it has become apparent that a new natural history is being defined in which some patients have substantial improvement following ERT, while others develop chronic disability reminiscent of the late-onset disease. In order to improve on the current clinical outcomes in Pompe patients with diminished clinical response to ERT, we sought to address the cause and potential for the treatment of disease manifestations which are not amenable to ERT. In this review, we will focus on the preclinical studies that are relevant to the development of a gene therapy strategy for Pompe disease, and have led to the first clinical trial of recombinant adeno-associated virus-mediated gene-based therapy for Pompe disease. We will cover the preliminary laboratory studies and rationale for a clinical trial, which is based on the treatment of the high rate of respiratory failure in the early-onset patients receiving ERT.

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Human Molecular Genetics

Recommended Citation

Byrne, B. j., Falk, D. J., Pacak, C. A., Nayak, S., Herzog, R. W., Elder, M. E., Collins, S. W., Conlon, T. J., Clement, N., Islam, S. (2011). Pompe disease gene therapy. Human Molecular Genetics, 20(R1), R61-R68.
Available at: https://ecommons.aku.edu/pakistan_fhs_mc_surg_paediatr/146